Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones

Abstract

Three gold(I) complexes of alkynyl chromones were synthesized and characterized. The single-crystal X-ray structure analysis of a dinuclear compound and of a flavone derivative exhibit a typical d 10 gold(I)-alkynyl linear arrangement. All complexes were evaluated as anticancer and antibacterial agents against four human cancer cell lines and four pathogenic bacterial strains. All compounds show antiproliferative activity at lower micromolar range concentrations. Complex 4 showed a broad activity profile, being more active than the reference drug auranofin against HepG2, MCF-7 and CCRF-CEM cancer cells. The cellular uptake into MCF-7 cells of the investigated complexes was measured by atomic absorption spectroscopy (AAS). These measurements showed a positive correlation between an increased cellular gold content and the incubation time of the complexes. Unexpectedly an opposite effect was observed for the most active compound. Biological assays revealed various molecular mechanisms for these compounds, comprising: (i) thioredoxin reductase (TrxR) inhibition, (ii) caspases-9 and -3 activation; (iii) DNA damaging activity and (iv) cell cycle disturbance. The gold(I) complexes were also bactericidal against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacterial strains, while showing no activity against the Gram-negative Escherichia coli bacterial strain.

Insights into the in vitro Anticancer Effects of Diruthenium‐1

“…Cytotoxicity assay:T he cytotoxicity was tested by as tandard MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (Sigma, St. Louis, MO, USA) microplate cell viability assay [95] with some modifications, as has been described in our previous work. [96] Cells were exposed to aw ide range of DiRu-1 concentrations (0.01-1 mm)f or 24 ha nd then cultured in drug-free medium for 48 h. The culture medium was used as an egative control (100 mL per well). At the end of the cell culture in drug-free medium, MTT (50 mL, 5mgmL À1 final concentration) was added to the appropriate microplate wells followed by a3hi ncubation at 37 8C.…”

Molecular Docking and PLIF Studies of Novel Tacrine-Naphtoquinone Hybrids Based on Multi-Target-Directed Ligand Approach for Alzheimer’s Disease

“…The 3 dimensional crystal structure of AChE (PDB ID: 1ACJ), BuChE (4BDS), and BACE-1 (1W51) were taken from a protein data bank (20). Water and co-crystal ligand molecules were eliminated from the structures and the PDBs were improved with regards to missing atom types by modeller 9.12 (21).…”

(Benzyl isocyanide)gold(I) pyrimidine‐2‐thiolate complex: Synthesis and biological activity

“…The presence of chloro group instead of thiolate ligand decreases the anti‐proliferative activity. Also, 2 displays higher cytotoxicity against MCF‐7 cell line than similar complexes such as phosphine‐bridged dinuclear Au(I) alkynyl, Au(I)–alkynyl chromones and Au(I)–carbene complexes …”